Vaccine 32 (2014) 1638–1639
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Discussion
The STI vaccine roadmap—A long overdue intervention Helen Rees a,∗ , King Holmes b a b
Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa Department of Global Health, University of Washington, Seattle WA, USA
The name herpes comes from the Greek meaning to ‘Creep and Crawl’, and centuries later Shakespeare referred to herpes as the ‘blister plague’. In the Middle Ages syphilis was treated with Mercury, leading to the expression that “a night in the arms of Venus means a lifetime spent on Mercury”. In the 19th century the symptoms of gonorrhoea were treated with silver nitrate and, early in the 20th century, syphilis with arsenicals. These were replaced by antibiotics that were so powerful that it was anticipated that the fight against syphilis, as well as against chlamydia, gonorrhoea and trichomoniasis was finally won. In the 21st century, resistance of Neisseria gonorrhoeae to all first line antimicrobials is now being encountered. Despite effective diagnostics and treatment, little progress is being made today in controlling chlamydial infection, and syphilis is again epidemic among men who have sex with men. Thus, despite the millennia of suffering that STIs have caused, and the enormous advances in diagnosis, treatment and cure, epidemics of syphilis, herpes, chlamydia, gonorrhoea and trichomoniasis continue, with concomitant pain, suffering and death. These STIs remain important causes of infertility, and maternal, perinatal, and neonatal morbidity. While the global response to other infectious diseases has been to prioritise the development of vaccines, there has been less evidence of this in the history of investment and scientific advance in STI vaccine development. Whether because of the scientific challenge, concerns about return on investment, or the social stigma attached to STIs, this area of R&D seems not to have enjoyed the same enthusiasm that has been shown for other vaccines. The two exceptions that could spark enthusiasm for STD vaccine research and development, and could galvanise stakeholders into renewed activity, are the remarkable success in development and introduction of hepatitis B vaccines and more recently of human papilloma virus vaccines. Although stigma and politics have somewhat slowed the roll-out of vaccines against these sexually transmitted pathogens, progress has nevertheless been steady, even in the United States, where there is already evidence of the impact of the HPV vaccine in reducing the spread of oncogenic HPV types. Population coverage has been very impressive in countries like Australia, Rwanda and Canada, where responsible political leadership has facilitated the marketing of HPV vaccine to protect
∗ Corresponding author. E-mail address: [email protected] (H. Rees). 0264-410X/$ – see front matter © 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.vaccine.2014.01.055
women. The uptake and impact of both hepatitis B and HPV vaccines demonstrate that, with a serious investment in science, a careful analysis of the public health need and of potential global markets, and with potential leadership breakthrough, development, manufacturing, and roll-out of STI vaccines can be achieved. The adoption of the Decade of Vaccines and the strategic direction laid out in the Global Vaccine Action Plan (GVAP) now provide us in 2014 with a global push towards new innovation in vaccine development for previously neglected diseases. The GVAP states that ‘New and improved vaccines are expected to become available during this decade, based on the robust vaccine pipeline that includes several products for diseases that are not currently preventable through vaccination.’ The GVAP emphasizes the importance of engaging with end users to prioritise vaccines and innovations according to perceived demand and added value. The WHO estimated that 500 million persons globally were newly infected in 2008 with Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, or Trichomonas vaginitis. The prevalence of HSV infection in 2003 has been estimated at over 530 million persons ages 15–49. There is little doubt that vaccines that would prevent these infections would be welcomed by these end users. The proposal of a roadmap for STI vaccine development is supported by the priorities within the GVAP and success in this initiative would also contribute to the relevance and prominence of the Decade of Vaccines as a meaningful intervention. Furthermore, the fields of vaccine development and public health partnerships are evolving. The reliance on big pharma alone to develop new vaccines is changing with the emergence of public–private partnerships. These partnerships, which engage public health institutions, donor agencies and academia, as well as the pharmaceutical industry, have the potential to create a new era for vaccine development. The PATH Malaria Vaccine Initiative is a successful demonstration of a partnership between an NGO, industry, academia, donors and government. It encompasses the development of RTS,S malaria vaccine candidates, translational research and demonstration projects. The vaccine investment strategy that has been undertaken by GAVI to evaluate the feasibility and cost effectiveness of introducing malaria vaccine within the next 5 years gives the partnering pharmaceutical companies an indication of the kind of advance market commitment that can be generated through GAVI support. Another example of a successful partnership is the Meningitis Vaccine Project that involved WHO and PATH with support from
H. Rees, K. Holmes / Vaccine 32 (2014) 1638–1639
the Bill and Melinda Gates Foundation. Not only did the scientists develop an effective and safe MenA conjugate vaccine, but the commitment of African governments within the meningitis belt to roll out the vaccine resulted in a dramatic reduction of Group A meningitis infections to almost negligible levels within a three year period. With their confidence boosted by this success, the countries involved are now aiming to eliminate Group A meningitis infection across the Meningitis Belt. The GVAP calls for the use of a new model to assist decisionmakers in prioritising investments in new vaccine; the model is based on health, economic, demographic, programmatic, and social impact criteria as well as scientific, technical and business opportunities. The data presented to the WHO’s STI Vaccine Consultation critically evaluated the potential for the development of vaccines to prevent infection from five common STI pathogens, namely herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, or Trichomonas vaginitis and/or the diseases they cause. The data unequivocally showed that development of vaccines to prevent all five infections could be justified using the GVAP criteria. Significant scientific advances have been made towards the development of vaccines for these five infections, development in herpes and chlamydial vaccine being the most advanced. Furthermore, the pharmaceutical industry has demonstrated interest in investing in the field. STIs have the unique advantage, compared to other vaccine preventable diseases, that there is a real likelihood of finding significant markets in both the developed and developing world: chlamydia, gonorrhoea, herpes and trichomoniasis are ubiquitous infections in all settings, although morbidity outcomes are clearly worse in poorer countries; and while congenital syphilis is still a challenge in the developing world, syphilis has also reemerged in the developed world amongst men who have sex with men. Putting all this together, we would argue that the investment case for the development of STI vaccines is a global imperative. Whilst the research for each potential vaccine is at different stage of development, there has been progress for all five diseases in understanding the innate and adaptive immune responses, and the
1639
immunologic and molecular and pathogenicity characteristics of the respective microbes. In the case of a herpes vaccine, partial effectiveness has already been demonstrated in women, opening up the real possibility that with persistence and investment an effective vaccine can be developed. The scientists attending the WHO consultation were keen to establish platforms for exchange of information on immunisation research and consensus building. So noting this progress, why would we abandon the research trajectory, particularly when the global thrust of the Decade of Vaccines is to stimulate investment in new vaccines for neglected diseases that cause significant morbidity and mortality? Furthermore the possible contribution of these five STIs to transmission of HIV, increases the public health arguments in favour of investment in these vaccines. The STI Vaccine Roadmap outlines the steps required to develop effective vaccines against some of the world’s most widespread sexually transmitted diseases. The demonstrated success of public–private partnerships in the field of vaccine development opens up new vistas for collaboration between key stakeholders. The engagement of donors and of GAVI in assessing the potential global market will create confidence for vaccine producers and investors. Sexually transmitted diseases should no longer be a class of disease that the world is willing to tolerate or conveniently ignore, but should be seen for what they are: diseases which can significantly affect people’s health and lives on an epidemic scale; and yet diseases which can be addressed by the development of effective vaccines if there is appropriate investment. The STI Vaccine Roadmap provides us with the strategy to do this, and this call to action should be supported by all those committed to public health and to the elimination of vaccine-preventable diseases. Disclaimer The authors alone are responsible for the views expressed in this article and do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.
Contents lists available at ScienceDirect
Vaccine journal homepage: www.elsevier.com/locate/vaccine
Discussion
The STI vaccine roadmap—A long overdue intervention Helen Rees a,∗ , King Holmes b a b
Wits Reproductive Health and HIV Institute, University of the Witwatersrand, Johannesburg, South Africa Department of Global Health, University of Washington, Seattle WA, USA
The name herpes comes from the Greek meaning to ‘Creep and Crawl’, and centuries later Shakespeare referred to herpes as the ‘blister plague’. In the Middle Ages syphilis was treated with Mercury, leading to the expression that “a night in the arms of Venus means a lifetime spent on Mercury”. In the 19th century the symptoms of gonorrhoea were treated with silver nitrate and, early in the 20th century, syphilis with arsenicals. These were replaced by antibiotics that were so powerful that it was anticipated that the fight against syphilis, as well as against chlamydia, gonorrhoea and trichomoniasis was finally won. In the 21st century, resistance of Neisseria gonorrhoeae to all first line antimicrobials is now being encountered. Despite effective diagnostics and treatment, little progress is being made today in controlling chlamydial infection, and syphilis is again epidemic among men who have sex with men. Thus, despite the millennia of suffering that STIs have caused, and the enormous advances in diagnosis, treatment and cure, epidemics of syphilis, herpes, chlamydia, gonorrhoea and trichomoniasis continue, with concomitant pain, suffering and death. These STIs remain important causes of infertility, and maternal, perinatal, and neonatal morbidity. While the global response to other infectious diseases has been to prioritise the development of vaccines, there has been less evidence of this in the history of investment and scientific advance in STI vaccine development. Whether because of the scientific challenge, concerns about return on investment, or the social stigma attached to STIs, this area of R&D seems not to have enjoyed the same enthusiasm that has been shown for other vaccines. The two exceptions that could spark enthusiasm for STD vaccine research and development, and could galvanise stakeholders into renewed activity, are the remarkable success in development and introduction of hepatitis B vaccines and more recently of human papilloma virus vaccines. Although stigma and politics have somewhat slowed the roll-out of vaccines against these sexually transmitted pathogens, progress has nevertheless been steady, even in the United States, where there is already evidence of the impact of the HPV vaccine in reducing the spread of oncogenic HPV types. Population coverage has been very impressive in countries like Australia, Rwanda and Canada, where responsible political leadership has facilitated the marketing of HPV vaccine to protect
∗ Corresponding author. E-mail address: [email protected] (H. Rees). 0264-410X/$ – see front matter © 2014 Published by Elsevier Ltd. http://dx.doi.org/10.1016/j.vaccine.2014.01.055
women. The uptake and impact of both hepatitis B and HPV vaccines demonstrate that, with a serious investment in science, a careful analysis of the public health need and of potential global markets, and with potential leadership breakthrough, development, manufacturing, and roll-out of STI vaccines can be achieved. The adoption of the Decade of Vaccines and the strategic direction laid out in the Global Vaccine Action Plan (GVAP) now provide us in 2014 with a global push towards new innovation in vaccine development for previously neglected diseases. The GVAP states that ‘New and improved vaccines are expected to become available during this decade, based on the robust vaccine pipeline that includes several products for diseases that are not currently preventable through vaccination.’ The GVAP emphasizes the importance of engaging with end users to prioritise vaccines and innovations according to perceived demand and added value. The WHO estimated that 500 million persons globally were newly infected in 2008 with Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, or Trichomonas vaginitis. The prevalence of HSV infection in 2003 has been estimated at over 530 million persons ages 15–49. There is little doubt that vaccines that would prevent these infections would be welcomed by these end users. The proposal of a roadmap for STI vaccine development is supported by the priorities within the GVAP and success in this initiative would also contribute to the relevance and prominence of the Decade of Vaccines as a meaningful intervention. Furthermore, the fields of vaccine development and public health partnerships are evolving. The reliance on big pharma alone to develop new vaccines is changing with the emergence of public–private partnerships. These partnerships, which engage public health institutions, donor agencies and academia, as well as the pharmaceutical industry, have the potential to create a new era for vaccine development. The PATH Malaria Vaccine Initiative is a successful demonstration of a partnership between an NGO, industry, academia, donors and government. It encompasses the development of RTS,S malaria vaccine candidates, translational research and demonstration projects. The vaccine investment strategy that has been undertaken by GAVI to evaluate the feasibility and cost effectiveness of introducing malaria vaccine within the next 5 years gives the partnering pharmaceutical companies an indication of the kind of advance market commitment that can be generated through GAVI support. Another example of a successful partnership is the Meningitis Vaccine Project that involved WHO and PATH with support from
H. Rees, K. Holmes / Vaccine 32 (2014) 1638–1639
the Bill and Melinda Gates Foundation. Not only did the scientists develop an effective and safe MenA conjugate vaccine, but the commitment of African governments within the meningitis belt to roll out the vaccine resulted in a dramatic reduction of Group A meningitis infections to almost negligible levels within a three year period. With their confidence boosted by this success, the countries involved are now aiming to eliminate Group A meningitis infection across the Meningitis Belt. The GVAP calls for the use of a new model to assist decisionmakers in prioritising investments in new vaccine; the model is based on health, economic, demographic, programmatic, and social impact criteria as well as scientific, technical and business opportunities. The data presented to the WHO’s STI Vaccine Consultation critically evaluated the potential for the development of vaccines to prevent infection from five common STI pathogens, namely herpes simplex virus, Chlamydia trachomatis, Neisseria gonorrhoeae, Treponema pallidum, or Trichomonas vaginitis and/or the diseases they cause. The data unequivocally showed that development of vaccines to prevent all five infections could be justified using the GVAP criteria. Significant scientific advances have been made towards the development of vaccines for these five infections, development in herpes and chlamydial vaccine being the most advanced. Furthermore, the pharmaceutical industry has demonstrated interest in investing in the field. STIs have the unique advantage, compared to other vaccine preventable diseases, that there is a real likelihood of finding significant markets in both the developed and developing world: chlamydia, gonorrhoea, herpes and trichomoniasis are ubiquitous infections in all settings, although morbidity outcomes are clearly worse in poorer countries; and while congenital syphilis is still a challenge in the developing world, syphilis has also reemerged in the developed world amongst men who have sex with men. Putting all this together, we would argue that the investment case for the development of STI vaccines is a global imperative. Whilst the research for each potential vaccine is at different stage of development, there has been progress for all five diseases in understanding the innate and adaptive immune responses, and the
1639
immunologic and molecular and pathogenicity characteristics of the respective microbes. In the case of a herpes vaccine, partial effectiveness has already been demonstrated in women, opening up the real possibility that with persistence and investment an effective vaccine can be developed. The scientists attending the WHO consultation were keen to establish platforms for exchange of information on immunisation research and consensus building. So noting this progress, why would we abandon the research trajectory, particularly when the global thrust of the Decade of Vaccines is to stimulate investment in new vaccines for neglected diseases that cause significant morbidity and mortality? Furthermore the possible contribution of these five STIs to transmission of HIV, increases the public health arguments in favour of investment in these vaccines. The STI Vaccine Roadmap outlines the steps required to develop effective vaccines against some of the world’s most widespread sexually transmitted diseases. The demonstrated success of public–private partnerships in the field of vaccine development opens up new vistas for collaboration between key stakeholders. The engagement of donors and of GAVI in assessing the potential global market will create confidence for vaccine producers and investors. Sexually transmitted diseases should no longer be a class of disease that the world is willing to tolerate or conveniently ignore, but should be seen for what they are: diseases which can significantly affect people’s health and lives on an epidemic scale; and yet diseases which can be addressed by the development of effective vaccines if there is appropriate investment. The STI Vaccine Roadmap provides us with the strategy to do this, and this call to action should be supported by all those committed to public health and to the elimination of vaccine-preventable diseases. Disclaimer The authors alone are responsible for the views expressed in this article and do not necessarily represent the views, decisions or policies of the institutions with which they are affiliated.
